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磁性UiO-66-NH核壳纳米杂化物作为槲皮素靶向递送至人乳腺癌细胞的有前景载体。

Magnetic UiO-66-NH Core-Shell Nanohybrid as a Promising Carrier for Quercetin Targeted Delivery toward Human Breast Cancer Cells.

作者信息

Parsaei Mozhgan, Akhbari Kamran

机构信息

School of Chemistry, College of Science, University of Tehran, 14155-6455 Tehran, Iran.

出版信息

ACS Omega. 2023 Oct 24;8(44):41321-41338. doi: 10.1021/acsomega.3c04863. eCollection 2023 Nov 7.

Abstract

In this study, a magnetic core-shell metal-organic framework (MOF) nanocomposite, FeO-COOH@UiO-66-NH, was synthesized for tumor-targeting drug delivery by incorporating carboxylate groups as functional groups onto ferrite nanoparticle surfaces, followed by fabrication of the UiO-66-NH shell using a facile self-assembly approach. The anticancer drug quercetin (QU) was loaded into the magnetic core-shell nanoparticles. The synthesized magnetic nanoparticles were comprehensively evaluated through multiple techniques, including FT-IR, PXRD, FE-SEM, TEM, EDX, BET, UV-vis, ZP, and VSM. Drug release investigations were conducted to investigate the release behavior of QU from the nanocomposite at two different pH values (7.4 and 5.4). The results revealed that QU@FeO-COOH@UiO-66-NH exhibited a high loading capacity of 43.1% and pH-dependent release behavior, maintaining sustained release characteristics over a prolonged duration of 11 days. Furthermore, cytotoxicity assays using the human breast cancer cell line MDA-MB-231 and the normal cell line HEK-293 were performed to evaluate the cytotoxic effects of QU, UiO-66-NH, FeO-COOH, FeO-COOH@UiO-66-NH, and QU@FeO-COOH@UiO-66-NH. Treatment with QU@FeO-COOH@UiO-66-NH substantially reduced the cell viability in cancerous MDA-MB-231 cells. Cellular uptake and cell death mechanisms were further investigated, demonstrating the internalization of QU@FeO-COOH@UiO-66-NH by cancer cells and the induction of cancer cell death through the apoptosis pathway. These findings highlight the considerable potential of FeO-COOH@UiO-66-NH as a targeted nanocarrier for the delivery of anticancer drugs.

摘要

在本研究中,通过将羧酸盐基团作为官能团引入铁氧体纳米颗粒表面,合成了一种磁性核壳金属有机框架(MOF)纳米复合材料FeO-COOH@UiO-66-NH,用于肿瘤靶向给药,随后采用简便的自组装方法制备UiO-66-NH壳层。将抗癌药物槲皮素(QU)负载到磁性核壳纳米颗粒中。通过多种技术对合成的磁性纳米颗粒进行了全面评估,包括傅里叶变换红外光谱(FT-IR)、粉末X射线衍射(PXRD)、场发射扫描电子显微镜(FE-SEM)、透射电子显微镜(TEM)、能量散射X射线光谱(EDX)、比表面积分析仪(BET)、紫外可见光谱(UV-vis)、ζ电位(ZP)和振动样品磁强计(VSM)。进行了药物释放研究,以研究QU在两种不同pH值(7.4和5.4)下从纳米复合材料中的释放行为。结果表明,QU@FeO-COOH@UiO-66-NH表现出43.1%的高负载量和pH依赖性释放行为,在长达11天的时间内保持持续释放特性。此外,使用人乳腺癌细胞系MDA-MB-231和正常细胞系HEK-293进行了细胞毒性试验,以评估QU、UiO-66-NH、FeO-COOH、FeO-COOH@UiO-66-NH和QU@FeO-COOH@UiO-66-NH的细胞毒性作用。用QU@FeO-COOH@UiO-66-NH处理显著降低了癌性MDA-MB-231细胞的细胞活力。进一步研究了细胞摄取和细胞死亡机制,证明癌细胞对QU@FeO-COOH@UiO-66-NH的内化以及通过凋亡途径诱导癌细胞死亡。这些发现突出了FeO-COOH@UiO-66-NH作为抗癌药物递送靶向纳米载体的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/741a/10633860/f628e9ef9069/ao3c04863_0013.jpg

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